Background: Concomitant oral administration of NFX with TNZ may affect NFX absorption and consequently its blood concentration and pharmacological effect. Objective: The present study was undertaken to investigate the effect of TNZ on the pharmacokinetics of NFX in healthy volunteers. Methods: This study was conducted as an open-label, randomized, two-way crossover experimental design. After an overnight fast, subjects were randomized to receive a single oral dose of NFX 400 mg alone and the fixed-dose combination (FDC) of NFX /TNZ 400 mg/600mg on two different occasions separated by 1-week washout period between treatments. The pharmacokinetic properties of NFX after FDC administration were compared with NFX administered alone. Results: The 90% CIs between NFX alone and when co-administered with TNZ indicated the presence of an interaction between NFX and TNZ, which would significantly increase the systemic rate and exposure of NFX absorption. The co-administration of TNZ with NFX increased the AUC and Cmax of NFX significantly compared with administration of NFX alone. Both Tmax and Ka of NFX showed a significant decrease after administration of the combination compared to administration of NFX alone. Conclusions: Both NFX and TNZ were well tolerated. The interaction of TNZ with fluroquinolones should be investigated to determine whether this interaction is limited to NFX or if other fluroquinolones have the same pharmacokinetic interactions. Further studies are necessary to determine the role of P-gp and other transporters on NFX disposition and pharmacokinetics. Additionally, the influence of TNZ on the physiological activity of GIT should be investigated.